Neurons and glia are derived from a common set of precursor stem cells. Morrow et al. used a cortical slice assay to examine the signals required to specify neuronal versus glial cell fate and differentiation. Dissociated embryonic neural stem cells from a green fluorescent protein (GFP)-expressing strain of mice were plated with cortical slices from mice of different ages (embryonic through postnatal). Cell fate and differentiation were monitored by changes in the morphology and expression of marker proteins for neurons and glia. Incubation of neural stem cells with embryonic cortical slices led to the development of mostly neuronal cells and incubation with postnatal cortical slices produced mostly glial cells, suggesting that different factors are produced at different stages of development and that the stem cells are poised to respond to either set of signals. Analysis of clones of the GFP-expressing cells showed that the signals were predominantly instructive and not trophic signals. The steps of glial cell fate specification and glial differentiation could be separated. The effects of postnatal cortical slices could be recapitulated by culture of the stem cells with fibroblast growth factor 2 (FGF2) and ciliary neurotrophic factor (CNTF), with FGF2 providing the signal for glial fate specification and CNTF providing the glial differentiation signal.
T. Morrow, M-R. Song, A. Ghosh, Sequential specification of neurons and glia by developmentally regulated extracellular factors. Development 128, 3585-3594 (2001). [Online Journal]